In particular, the instant invention is related to light-emitting systems used for photo-dynamic therapy.
Photodynamic therapy (PDT) is a non-thermal technique which can be used to produce localised tissue necrosis. This requires activating a photosensitizer with light of a specific wavelength to form a cytotoxic species from molecular oxygen (mostly singlet oxygen). For a photodynamic reaction to occur, the photosensitizer, activating light and oxygen must be present in sufficient amounts.
The photosensitizer could be synthesized endogenously under the influence of a pre-administered precursor. The formation of the cytotoxic species requires the pre-administration of a species, which, below, is generally called the “drug”.
The therapeutic effect of photodynamic therapy depends on a combination of parameters that include drug dose, drug-light interval, oxygen and light fluence rate. It also varies according to the wavelength distribution of the light source. Finally, a homogeneous and reproducible fluence rate delivery during clinical PDT is determinant in preventing under- or overtreatment. In dermatology, topical PDT has been carried out with a wide variety of light sources delivering a broad range of light doses. Irradiance is usually limited to less than 100 mW·cm−2.
Light-emitting diodes (LEDs) are now considered as an appropriate light source for PDT. Indeed, LEDs have a relatively narrow bandwidth (usually 20 to 30 nm) and are available in a wide range of wavelengths. LED systems for Methyl aminolevulinate PDT (MAL-PDT) such as Aktilite® CL 16 and Aktilite® CL 128 (Metvix, Galderma) are now mainly used. The Aktilite® CL 16 treats areas of skin measuring 40×50 mm whereas the Aktilite® CL 128 treats larger areas (80×180 mm). They provide light doses of 37 J·cm−2 required for the optimal activation of the associated photosensitizer. Fluence rate varies between 70 and 100 mW·cm−2, for an irradiation time varying between 6 and 10 minutes. However even commercial systems, such as Aktilite® CL 16, do not deliver a uniform light distribution (Moseley, 2005). In the case of the CL 16, the irradiance may be as low as 38% of the central area at a distance of only 2 cm. These measurements were made on a flat surface. The heterogeneity is even greater during illumination of curved surfaces (face or scalp).
Thus, a homogeneous and reproducible fluence delivery rate during clinical photodynamic therapy plays a determinant role in preventing under- or over-treatment. Photodynamic therapy applied in dermatology has been carried out with a wide variety of light sources delivering a broad range of more or less adapted light doses. Due to the complexity of human anatomy, such as the human face and also vulval, and perianal areas, these light sources do not in fact deliver a uniform light distribution to the skin.
In dermatology, the clinical use of 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX) for photodynamic therapy is proposed for non-melanoma skin cancer treatment. However, this treatment is painful, limiting the suitability of photodynamic therapy as a treatment of first choice. Patients report a burning or tingling sensation that sometimes leads to need for local anesthesia or termination of therapy. Especially treating extensive field cancerization with actinic keratosis in the face and scalp region is painful for the patient.
One way to reduce the pain consists in light dose fractionation. Irradiation is interrupted at a particular point for a period of time. There is therefore a succession of illumination periods and of rest periods. Besides, light fractionation also increases the efficiency: light fractionation produces more necrosis than with the same light dose delivered without rest periods.
Conventional light sources necessary for photodynamic therapy are expensive. Therefore an inactive or rest period is a waste of medical means.
Consequently the use of PDT has largely been limited to hospital outpatient services where costs can be high and the service inconvenient for the patient.
New concepts in illumination, such as ambulatory PDT or daylight illumination might contribute to the further acceptance of this method.
Additionally, actinic keratosis (AK) are scaly or crusty growths (lesions) caused by damage from the sun's ultraviolet rays (UVR). Actinic Keratosis is also known as solar keratosis. Untreated actinic keratosis can advance to squamous cell carcinoma (SCC), the second most common form of skin cancer. Treatment options include ablative (destructive) therapies such as cryosurgery, curettage with electrosurgery, and photodynamic therapy. Topical photodynamic therapy for actinic keratosis is now a well established treatment modality, with two drugs registered for this indication. In the last years, new formulations have been developed, which promise a further improvement of actinic keratosis treatment. Photodynamic therapy is well tolerated, has excellent cosmetic results, and has reported cure rates between 69 and 93%, with fewer side effects compared to the other treatment options. Presently, a flat LED panel is used as light source.
A conventional protocol using Metvix® (methyl aminolevulinate) consists in having Metvix® specifically absorbed into the altered skin cells of these lesions. Metvix® causes compounds called porphyrins to accumulate and be absorbed selectively by the actinic keratosis. Metvix® is applied to the lesions to be treated. The lesion is covered with a dressing. There is a 3 hour waiting period for the Metvix® cream to be absorbed and metabolized. After 3 hours, Metvix® is washed off and the patient is immediately illuminated with a red light, the intensity and time exposed to red light depends on the type of lesions that are treated. Light exposure can last between 8-20 minutes. The illumination is not homogeneous since a LED panel is used.
The size and the design of the led panel are not appropriate for bald scalps. Since the treatment is performed in a short period of time, the treatment is usually very painful.
One challenge in order to ensure the development of such treatment is to guarantee a uniform light illumination of the skin due to the complexity of the human anatomy.
Now the present inventors have developed a new medical device which allows delivering a uniform light distribution to complex body shapes and high fluence rate of illumination. Indeed, the development of flexible light sources considerably improves the homogeneity of light delivery. The integration of plastic optical fibres into textile structures offers an interesting alternative to rigid light emitters. It has also been shown that such light-emitting textiles do not heat at all, which enables their use for a long time by the patient.
However, one remaining factor which still limits the use of ambulatory PDT is the long time necessary to obtain sufficient amounts of the photosensitizer. One strives to reduce this time.